首页> 外文期刊>Neuroscience: An International Journal under the Editorial Direction of IBRO >Cloning and molecular characterization of the orphan carrier protein Slc10a4: expression in cholinergic neurons of the rat central nervous system.
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Cloning and molecular characterization of the orphan carrier protein Slc10a4: expression in cholinergic neurons of the rat central nervous system.

机译:孤儿载体蛋白Slc10a4的克隆和分子表征:在大鼠中枢神经系统胆碱能神经元中的表达。

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We report on the cloning and molecular characterization of the rat carrier Slc10a4 and its cellular localization in the CNS by immunohistochemistry. Slc10a4 is the rat counterpart of the human orphan carrier SLC10A4, which was recently reported to be highly expressed in brain and placenta. Both carriers belong to the solute carrier family SLC10, formerly named the "sodium/bile acid cotransporter family." So SLC10A4/Slc10a4 has a phylogenetic relationship to the Na+/taurocholate cotransporting polypeptide Ntcp (Slc10a1) and the apical sodium-dependent bile acid transporter Asbt (Slc10a2). The rat Slc10a4 protein consists of 437 amino acids and exhibits a seven transmembrane domain topology with N(exo)/C(cyt)trans-orientation of the N- and C-terminal ends. Expression of the Slc10a4 protein was detected in motor regions of the spinal cord and rhombencephalon, as well as in mesopontine cholinergic neurons, the medial habenula, cholinergic areas of the forebrain, and the gut myenteric plexus. Co-localization studies with the cholinergic marker proteins choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), and high-affinity choline transporter (CHT1) demonstrated expression of Slc10a4 in cholinergic neurons. Despite its close phylogenetic relationship to Ntcp, Slc10a4 showed no transport activity for the Ntcp substrates taurocholate, estrone-3-sulfate, dehydroepiandrosterone sulfate, and pregnenolone sulfate when expressed in HEK293 cells or Xenopus laevis oocytes. Slc10a4 also did not transport choline, which is a substrate of CHT1. Although the functional properties of Slc10a4 could not be elucidated in this study, Slc10a4 is regarded as a new marker protein for cholinergic neurons in the rat CNS.
机译:我们报告了大鼠免疫球蛋白Slc10a4的克隆和分子特征及其在中枢神经系统中的细胞定位。 Slc10a4是人类孤儿载体SLC10A4的大鼠对应物,最近据报道它在脑和胎盘中高度表达。两种载体均属于溶质载体家族SLC10,以前称为“钠/胆汁酸共转运蛋白家族”。因此,SLC10A4 / Slc10a4与Na + /牛磺胆酸盐共转运多肽Ntcp(Slc10a1)和根尖钠依赖性胆汁酸转运蛋白Asbt(Slc10a2)有系统发育关系。大鼠Slc10a4蛋白由437个氨基酸组成,表现出七个跨膜结构域拓扑结构,其中N和C末端具有N(exo)/ C(cyt)反方向。 Slc10a4蛋白的表达在脊髓和菱形脑的运动区域以及中桥蛋白胆碱能神经元,内侧and,前脑胆碱能区域和肠肌层神经丛中检测到。与胆碱能标记蛋白胆碱乙酰基转移酶(ChAT),囊泡乙酰胆碱转运蛋白(VAChT)和高亲和力胆碱转运蛋白(CHT1)的共定位研究证明了Slc10a4在胆碱能神经元中的表达。尽管Slc10a4与Ntcp有密切的系统发育关系,但在HEK293细胞或非洲爪蟾卵母细胞中表达时,对Ntcp底物牛磺胆酸盐,雌酮-3-硫酸盐,脱氢表雄酮硫酸盐和孕烯醇酮硫酸盐没有显示转运活性。 Slc10a4也没有转运胆碱,胆碱是CHT1的底物。尽管在这项研究中无法阐明Slc10a4的功能特性,但Slc10a4被认为是大鼠中枢神经系统胆碱能神经元的新标记蛋白。

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